Kyoto University

Nahls Corporation Co., Ltd.

Bunta Watanabe

Ryuzo Yoshioka

Hideaki Ishida

Jun Hiratake

A novel compound has pharmacological activities comparable to those of Nahlsgen and is storable excellently stably. The compound can be produced by a method according to the present invention for producing an optically active 2-amino-phosphonoalkanoic acid salt. In the method, a starting material DL-2-amino-phosphonoalkanoic acid represented by Formula (1) or a hydrate thereof is reacted with an optically active basic compound other than an optically active lysine, to give a diastereomeric salt mixture including a first salt (including a hydrate salt) between a D-2-amino-phosphonoalkanoic acid represented by Formula (1-1) and the optically active basic compound, and a second salt (including a hydrate salt) between an L-2-amino-phosphonoalkanoic acid represented by Formula (1-2) and the optically active basic compound. The diastereomeric salt mixture is fractionally crystallized to isolate one of the first and second diastereomeric salts.

Optically-active 2-amino-phosphonoalkane acid, optically-active 2-amino-phosphonoalkane acid salt, and hydrates of these

A novel compound has pharmacological activities comparable to those of Nahlsgen and is storable excellently stably. The compound can be produced by a method according to the present invention for producing an optically active 2-amino-phosphonoalkanoic acid salt. In the method, a starting material DL-2-amino-phosphonoalkanoic acid represented by Formula (1) or a hydrate thereof is reacted with an optically active basic compound other than an optically active lysine, to give a diastereomeric salt mixture including a first salt (including a hydrate salt) between a D-2-amino-phosphonoalkanoic acid represented by Formula (1-1) and the optically active basic compound, and a second salt (including a hydrate salt) between an L-2-amino-phosphonoalkanoic acid represented by Formula (1-2) and the optically active basic compound. The diastereomeric salt mixture is fractionally crystallized to isolate one of the first and second diastereomeric salts. 

Provided is a method for separating the four optical isomers of Nahlsgen. The method according to the present invention for producing a mixture of a D-2-amino-4-[(Rp)-(3-carboxymethylphenoxy)(methoxy)phosphoryl]butanoic acid hydrate and an L-2-amino-4-[(Sp)-(3-carboxymethylphenoxy)(methoxy)phosphoryl]butanoic acid hydrate includes subjecting a mixture of the four optical isomers, represented by Formula (1'), to fractional crystallization from water or from a solvent mixture of water and a water-soluble organic solvent, to precipitate a mixture of a compound represented by Formula (1-1&#x2032;-1) and a compound represented by Formula (1-4&#x2032;-1), where Formulae (1&#x2032;), (1-1&#x2032;-1), and (1-4&#x2032;-1) are expressed as follows: 

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Kyoto, Japan

Bunta Watanabe